Liver fibrosis: Direct antifibrotic agents and targeted therapies

肝星状细胞 医学 纤维化 肝硬化 癌症研究 肝病 慢性肝病 细胞外基质 免疫学 生物信息学 病理 内科学 生物 细胞生物学
作者
Detlef Schuppan,Muhammad Ashfaq–Khan,Ai Ting Yang,Yong Oock Kim
出处
期刊:Matrix Biology [Elsevier]
卷期号:68-69: 435-451 被引量:350
标识
DOI:10.1016/j.matbio.2018.04.006
摘要

Liver fibrosis and in particular cirrhosis are the major causes of morbidity and mortality of patients with chronic liver disease. Their prevention or reversal have become major endpoints in clinical trials with novel liver specific drugs. Remarkable progress has been made with therapies that efficiently address the cause of the underlying liver disease, as in chronic hepatitis B and C. Highly effective antiviral therapy can prevent progression or even induce reversal in the majority of patients, but such treatment remains elusive for the majority of liver patients with advanced alcoholic or nonalcoholic steatohepatitis, genetic or autoimmune liver diseases. Moreover, drugs that would speed up fibrosis reversal are needed for patients with cirrhosis, since even with effective causal therapy reversal is slow or the disease may further progress. Therefore, highly efficient and specific antifibrotic agents are needed that can address advanced fibrosis, i.e., the detrimental downstream result of all chronic liver diseases. This review discusses targeted antifibrotic therapies that address molecules and mechanisms that are central to fibrogenesis or fibrolysis, including strategies that allow targeting of activated hepatic stellate cells and myofibroblasts and other fibrogenic effector cells. Focus is on collagen synthesis, integrins and cells and mechanisms specific including specific downregulation of TGFbeta signaling, major extracellular matrix (ECM) components, ECM-crosslinking, and ECM-receptors such as integrins and discoidin domain receptors, ECM-crosslinking and methods for targeted delivery of small interfering RNA, antisense oligonucleotides and small molecules to increase potency and reduce side effects. With an increased understanding of the biology of the ECM and liver fibrosis and an improved preclinical validation, the translation of these approaches to the clinic is currently ongoing. Application to patients with liver fibrosis and a personalized treatment is tightly linked to the development of noninvasive biomarkers of fibrosis, fibrogenesis and fibrolysis.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
天真茗发布了新的文献求助40
1秒前
情怀应助tracer采纳,获得30
1秒前
陈法国发布了新的文献求助10
1秒前
CodeCraft应助圆滑的铁勺采纳,获得10
2秒前
3秒前
慕青应助光亮芷采纳,获得10
3秒前
汉堡包应助寒冷的奇异果采纳,获得10
4秒前
pangmengxuan发布了新的文献求助10
5秒前
快乐小狗发布了新的文献求助10
5秒前
zoro完成签到,获得积分10
5秒前
sxwzssyj完成签到,获得积分10
6秒前
争取不秃顶的医学僧完成签到,获得积分10
7秒前
海猫食堂完成签到,获得积分10
8秒前
猫子戏法完成签到,获得积分20
9秒前
10秒前
11秒前
慧海拾穗完成签到 ,获得积分10
11秒前
11秒前
Liziqi823发布了新的文献求助10
11秒前
13秒前
Orange应助pangmengxuan采纳,获得10
13秒前
14秒前
小王八完成签到 ,获得积分10
14秒前
14秒前
CodeCraft应助xxxx采纳,获得30
14秒前
陈法国完成签到,获得积分20
15秒前
猫子戏法发布了新的文献求助10
15秒前
孙孙应助快乐小狗采纳,获得10
15秒前
15秒前
Yang完成签到,获得积分10
15秒前
无私的问芙完成签到,获得积分10
16秒前
16秒前
郑波涛发布了新的文献求助10
17秒前
18秒前
领导范儿应助YUNJIE采纳,获得10
19秒前
19秒前
彭于晏应助怕黑斑马采纳,获得10
19秒前
20秒前
小张z完成签到,获得积分10
20秒前
玄月发布了新的文献求助10
21秒前
高分求助中
Sustainability in Tides Chemistry 2000
The ACS Guide to Scholarly Communication 2000
Studien zur Ideengeschichte der Gesetzgebung 1000
TM 5-855-1(Fundamentals of protective design for conventional weapons) 1000
Threaded Harmony: A Sustainable Approach to Fashion 810
Pharmacogenomics: Applications to Patient Care, Third Edition 800
Gerard de Lairesse : an artist between stage and studio 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3076389
求助须知:如何正确求助?哪些是违规求助? 2729242
关于积分的说明 7508108
捐赠科研通 2377477
什么是DOI,文献DOI怎么找? 1260632
科研通“疑难数据库(出版商)”最低求助积分说明 611101
版权声明 597194